Cyclopentenyl substituted aliphatic acids



Patented July 24, 1928,

UNITED STATES 1,678,175 PATENT OFFICE.

ROGER ADAMS, OF URBANA, ILLINOIS; CARL R. NOLLEIQOF ST. LOUIS, MISSOURI AND JAMES A. ARITIN, E URBANA, ILLINOIS, ASSIGNORS TO ABBOTT LABORATORIES,

OF NORTH CHICAGO, -ILLINOIS, A CORPORATION ILLINOIS.

\ CYCLOIENTENYL SUBSTITUTED ALIPHATIC ACIDS.

No Drawing.

' The invention relates to. certain racemic aliphatic acids and their derivatives in which the omega carbon atom is substituted by a delta-2-cyclopentenyl group. The acids 5 and their derivatives which have been prepared and which have been found useful in medicine, particularly in the treatment of diseases produced by B. Leprae or B.Tuberculoci, have the general formula- CH=CH bn-cm-(onvnoooz Hz-CH:

in which Y represents a monovalent atom or group, such as hydrogen, hydroxyl, halogen, carboxyl, etc.; X represents one or more; and Z represents hydrogen or a sub stituted hydrogen, such 'as a metal or. an alkyl group.

These compounds are optically inactive, as

the dextro and.levo-rotatory. forms are produced in equal amounts by the synthesis, giving rise in the case of each compound to a racemic modification.

, A number of available methods may be 0 employed for the preparation of these compounds; to serve as illustrations, a few applicable methods for certain members of the series are described. The acids containing from 2 to 8 carbons inclusivein'the side chain may be prepared by the malonic ester synthesis. For example, cyclopentenyl ethyl bromide is converted into the Grignard derivative and treated with aldehydo-octanoate to give the hydroxy d-l-hydnocarpic acid ester. Another-method which may beem;

ployed for the synthesis of a lower member of the series, as cyclopentenyl butano1c acid,

consists in condensing cyclopentenyl ethyl bromide with monosodium' malomc ester, 40 and heating to eliminate carbon dioxide.

E EXA PLES. I Methyl hydrowy d-l-ltydnocarpate.

I Cyclopentenyl ethyl bromide ma be prepared as follows A solution 0 62.5 gr. of cyclopentenyl ethanol in 150 cc. dry tolu one is cooled to 5 C. and a solution of g. of redistilled phosphorus tribromide in 50 100 cc. toluene run in, keeping the temperature below 0 C. The mixture is then allowed to warm to room temperature and ii nally heated on the steam bath for one hour. Coo pour into water, dry the toluene layer,

Application filed July 9, 1927. Serial No. 204,658.

and distill. The cyclopentenyl ethyl bromide so obtained boils at 71-72 C. (uncorn) under 16 mm. pressure.

A dry ether solution of 157.5 grams cyclo- Y pentenyl ethyl bromide is converted into cyclopentenyl ethyl magnesium bromide, and

the Grignard reagent diluted with dry ether to 1200 cc. This product is condensed with 186 grams of methyl 8-aldehydo-octanoate, and the resulting product decomposed with Water. Methyl Q-hydroxy d-l-hydnocarpate is thus obtained as .Q-hyolromy d-l-hg dnocarpz'c acid.

The above ester may be saponified by alcoholic potassium hydroxide to' Q-hydroxy d-l-hydnocarpic acid, which, after recrystallization from acetone, melts at 62.0-62.8 C. (corn).

UyclopentenjI/Z ethyl malonic ester.

OyOZopenteng Z ethyl malonic acid When the above ester is saponified with aqueous sodium hydroxide solution, and the acid obtained therefrom recrystallized from benzene, there is obtained cyclopentenyl ethyl malonic acid, as colorless crystals, mp. 107-- 107.5 C. (corn).

Cyclopentehylbutanoie acid.

an oil, which boils at. 177179 (uncorr.) at 2 mm.

clopentenylbutyric acid so obtained boils at 125126 0. (corn) at 4 mm. pressure.

The scope of the invention should be determined by reference to the appended "claims, said claims being construed as broad-.

v 1y as possible, consistent with the state of 2. New eompounds of. the formula the art. OH=CH We claim as-our invention: $3 0114011910002 1. New compounds of the formula om-on/ 5 5 1 in which X represents one or more, and Z /CH OHACHYk represents hydrogen or a substituted hydro- QHFCH gen such as ametallie element or alkyl. in which Y representsa monovalent atom or group, X represents one or more, and Z rep- ROGER ADAMS. resents hydrogen or a substituted hydrogen, CARL R. NOLLER.

such as a metal or an alkyl group. JAMES A. ARVIN. 

